tbuckley/cabot-search huggingface dataset:
Abstract P1-05-26: A blood-based lipid panel for personalized risk assessment of breast cancer
Authors: Johannes Fahrmann, Ehsan Irajizad, Jody Vykoukal, Angelica Gutierrez Barrera, Jennifer Dennison, Ranran Wu, Banu K. Arun, Abenaa Brewster, Samir Hanash
Journal: Cancer Research (2023)

Abstract Background: The metabolic syndrome characterized in part by obesity, hyperinsulinemia, and insulin resistance is associated with increased risk of breast cancer. However there remains a need to establish a circulating biomarker metabolic profile indicative of increased risk of breast cancer. In the current study, we performed a comprehensive metabolomics screen to identify biomarkers indicative of increased risk of breast cancer. Methods: Unbiased metabolomics profiling was conducted on an initial Development Set of plasmas collected from 353 newly-diagnosed breast cancer cases and 141 controls. A deep learning neural network with 3 layers each containing 32 nodes based on 11 individual lipids corresponding to discrete lipid subclasses was built for risk prediction of breast cancer. The model was validated in an independent Test Set consisting of 79 breast cancer cases and 163 controls. Using a nested case:control matched design, we evaluated the performance of the model among body mass index (BMI) strata (≥ 30 or &amp;lt; 30kg/m2). Results: An 11-marker lipid biomarker panel encompassing lipid subclasses with known pro-inflammatory and tumor promoting roles yielded an AUC of 0.75 (95% CI: 0.70-0.79) for distinguishing breast cancer cases from controls in the Development Set. Predictive performance of the lipid panel was comparable when stratifying cases into hormone-receptor (HR) positive, HER2-positive/HR negative, and triple-negative breast cancer subtypes. The biomarker panel had an AUC of 0.74 (95% CI: 0.68-0.81) in the independent Test Set. The predictive performance of the panel was most pronounced among obese subjects (BMI ≥ 30) with an AUC of 0.81 (95% CI: 0.71-0.91) in the Test Set. Conclusions: The lipid-based biomarker panel has utility for identifying women with ‘metabolic obesity’ who are at increased risk of breast cancer and would benefit from tailored screening. Citation Format: Johannes Fahrmann, Ehsan Irajizad, Jody Vykoukal, Angelica Gutierrez Barrera, Jennifer Dennison, Ranran Wu, Banu K. Arun, Abenaa Brewster, Samir Hanash. A blood-based lipid panel for personalized risk assessment of breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-26.
Abstract ED4-2: Metaplastic Breast Cancer
Authors: Alexandra Thomas
Journal: Cancer Research (2023)

Abstract Metaplastic breast cancer (MPC) is a less common subtype of breast cancer, representing approximately 0.2-0.5% of breast cancer diagnoses, which is often associated with poor outcomes. MPC is an overarching term for breast tumors which demonstrate differentiation toward epithelial or mesenchymal components, or a mixture of these. In the context of challenging subtypes of breast cancer, thiseducational discussion will review epidemiology and clinical course of these tumors. Molecular characteristics of MPC and how this might impact current, as well as possible future, management strategies will be discussed. Finally, opportunities for laboratory investigations and clinical trial approaches to further understand and better treat MPC will also be discussed. Citation Format: Alexandra Thomas. Metaplastic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED4-2.
Abstract ED13-2: Radiation therapy and cardiovascular disease in breast cancer
Authors: Carmen Bergom
Journal: Cancer Research (2023)

Abstract This presentation will review the topic of radiation-induced cardiac dysfunction in patients with breast cancer. Specific areas of discussion include the a review of the cardiac-sparing techniques available for radiation therapy in breast cancer treatment; guidelines for the prevention, diagnosis, and treatment of cardiac dysfunction after radiation exposure in patients with breast cancer; and new areas of research in the field of radiation-induced cardiac disease in breast cancer. Emerging knowledge of how concurrent systemic therapies may interact with radiation to affect heart function will also be discussed. In addition, future directions in the field of radiation-induced heart dysfunction will be reviewed. Citation Format: Carmen Bergom. Radiation therapy and cardiovascular disease in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED13-2.
Abstract ED1-4: Patient Advocate Perspective
Authors: Patty Spears
Journal: Cancer Research (2023)

Abstract Patient reported outcome (PRO) measures can be collected in clinical trials or clinical care through questionnaires. PROs allow a direct measure of how a patient is feeling and functioning, directly from the patient without interpretation by another person or clinician. PROs give patients a voice. Although there are challenges to collecting PROs, these challenges can be overcome. When deciding which measures to collect there are some things to keep in mind. For example, if the questions are relevant and meaningful to what the patient is experiencing they will be more likely to fill them out, providing useful information. The questionnaires can also be given in multiple formats (electronic, paper, telephone) to accommodate the preferences of different patients. However, collecting PROs is not enough, the information collected needs to be used to inform future patients or inform patient care. Additional challenges and benefits of collecting PROs in breast cancer research and clinical care from the patient perspective will be discussed. Citation Format: Patty Spears. Patient Advocate Perspective [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED1-4.
Abstract P1-13-12: Targeting Dynamin-related protein 1 for the management of taxane-resistant triple-negative breast cancer
Authors: David Terrero, Amit Tiwari, Dayanidhi Raman
Journal: Cancer Research (2023)

Abstract The development of drug resistance is a primary cause of chemotherapy failure in the treatment of triple-negative breast cancer (TNBC). Some cancer cells are resistant to drugs with unrelated structures and mechanisms of action, a phenomenon known as multidrug resistance (MDR). Although taxanes such as docetaxel and paclitaxel are effective against non-metastatic and metastatic TNBC and other types of breast cancer, they eventually become ineffective due to development of drug resistance. Mitochondrial dynamics has gained significant attention as a means to treat MDR and non-MDR cancers. Mitochondrial dynamics determine the number, shape, and location of mitochondria within cells, which are fundamental to the health of the cell. Among its key components is the mitochondrial fission-promoting dynamin-related protein 1 (Drp1). There is mounting evidence indicating that both Drp1 and its phosphorylated form promote cancer survival, resistance to apoptosis, and chemoresistance. We observed increased phosphorylation of Drp1 at Ser616 as well as phosphorylation of its upstream kinase ERK1/2 in TNBC lines SUM159PT and its paclitaxel-resistant derivative that we developed called SUM159PT/PAC200 that displays more than an 80-fold increase in resistance to paclitaxel. Using CRISPR-Cas9 technology, we knocked out the gene encoding Drp1 in both lines. When Drp1 is genetically ablated, paclitaxel resistance in SUM159PT/PAC200 was significantly reversed. Furthermore, proliferation, migration, and invasion capabilities were decreased in both parental and paclitaxel-resistant Drp1 knockout lines. In SUM159PT/PAC200 Drp1-KO cells, a mesenchymal to epithelial transition (MET) was observed as indicated by downregulation of mesenchymal markers such as N-cadherin and -catenin, and upregulation of the epithelial marker ZO-1. Interestingly, Drp1 knockout halted the ability of SUM159PT/PAC200 to form colonies in soft agar. SUM159PT/PAC200 cells strongly express the MDR pump P-glycoprotein (ABCB1), to which paclitaxel is a known substrate, and genetically targeting Drp1 reduced the expression to almost undetectable levels. Taken together, these findings suggest that Drp1 is both a resistance factor and a key protein in breast cancer proliferation and dissemination, making it a promising actionable molecular target in the treatment of TNBC. Further studies are in progress to understand the role of Drp1 in the development and maintenance of MDR phenotype, proliferation, and invasion. Citation Format: David Terrero, Amit Tiwari, Dayanidhi Raman. Targeting Dynamin-related protein 1 for the management of taxane-resistant triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-13-12.
Abstract ED1-2: How to incorporate PROs into clinical care
Authors: Oluwadamilola (Lola) Fayanju
Journal: Cancer Research (2023)

Abstract Patient-reported outcomes (PROs) are self-reported assessments of health status that come from the patient’s perspective. Communicated without interpretation by a physician, PROs can enhance shared-decision making. When administered in multi-lingual, level-appropriate, and culturally aware formats, PROs can be used to address the individual and collective health status of potentially vulnerable groups including children, older adults, those with disabilities, and those from racial/ethnic minority backgrounds thereby providing an opportunity not only to address the needs of individuals but also identify potential disparities across groups. In her talk, Dr. Fayanju will provide strategies to facilitate incorporation of PROs into routine patient care and describe the benefits and potential challenges associated with doing so. Citation Format: Oluwadamilola (Lola) Fayanju. How to incorporate PROs into clinical care [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED1-2.
Abstract ED4-3: Inflammatory Breast Cancer
Authors: Filipa Lynce
Journal: Cancer Research (2023)

Abstract Inflammatory Breast Cancer (IBC) has an incidence of 1-5% among all breast cancers diagnosed within the USA, yet it accounts for a disproportionately high rate of mortality, leading to up to 10% of all breast cancer related deaths. Although IBC can present with any receptor status in terms of estrogen, progesterone, and human epidermal growth factor 2 (HER2), there is a higher proportion of HER2 positive cases compared to non-IBC. Given the distinct difference in outcome, it is important to differentiate IBC from more indolent locally advanced non-IBC with secondary inflammatory features. Despite ongoing efforts to identify molecular markers specific for IBC, the underlying tumor biology and genomic drivers of progression remain largely unknown. In this session we will review tumor-intrinsic signaling pathways, the role of the tumor microenvironment and clinical trials with combination therapies to inform future biomarkers of disease progression in IBC. Citation Format: Filipa Lynce. Inflammatory Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED4-3.
Abstract ED5-3: Financial toxicity
Authors: Fumiko Chino
Journal: Cancer Research (2023)

Abstract People with cancer spend more out of pocket for medical care than others with chronic diseases, a pattern that persists years after initial cancer diagnosis and treatment. Patients and their families are at risk for financial toxicity including problems paying medical bills, increased stress and/or symptom burden, and delaying or forgoing care due to costs. In this talk, Dr. Fumiko Chino provides an overview of financial toxicity in cancer care and its real-life impact on people with cancer. Factors contributing to financial toxicity are addressed as well potential solutions. 1. Define financial toxicity as a negative consequence of cancer diagnosis/treatment 2. Describe effects of financial toxicity on quality of life, adherence, and outcomes 3. Name potential solutions to financial toxicity on a health system, provider, and patient level Citation Format: Fumiko Chino. Financial toxicity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED5-3.
Abstract ED1-3: Where are we going with digital interventions and PROs
Authors: Ines Vaz Luis
Journal: Cancer Research (2023)

Abstract Rational: Lately, digital health has shown potential to facilitate cancer care delivery. We now have data that demonstrated that systems integrating self-reporting of common symptoms during treatment for both adjuvant and metastatic breast cancer treatment and allowing for patient remote monitoring result not only result in better quality of life and less emergency room visits, but, in some settings, also lead to significant survival benefit. In addition, some studies incorporating self-management strategies that do not need heavy clinician involvement have shown promising results to manage acute and long and late term physical, social, and psychological effects of cancer and its treatment. Objectives: In this talk, we will 1) review data on the existing digital health solutions that can be used in clinical care. In addition, 2) we will reflect on what is next in digital health innovation, particularly a) how the integration of technology, including digital companions facilitating remote monitoring, education and self-management, may serve as a vehicle to promote continuous care b) innovative emerging digital health tools (including, although not limited to wearables and digital therapeutics).Finally, 3) we will examine how digital health can address the needs of every patient, avoid pitfalls such as contributing to health disparities. Citation Format: Ines Vaz Luis. Where are we going with digital interventions and PROs [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED1-3.
Abstract ED12-2: Mechanisms of sensitivity and resistance to HRD targeting agents in breast cancer – PARPi and beyond
Authors: Christopher Lord
Journal: Cancer Research (2023)

Abstract Although PARP inhibitors (PARPi) deliver significant and sustained anti-tumour responses in those with HR defective cancers, PARPi resistance is a common clinical phenomenon and limits the overall effectiveness of these agents. I will discuss how reversion mutations in BRCA1 and BRCA2 cause PARPi resistance and how the emergence of reversions might be targeted by immune responses against the neopeptides caused by reversion mutations. I will also discuss how other mechanisms of PARPi resistance such as 53BP1/Shieldin complex dysfunction could be targeted by evolutionary “double binds” using drugs such as Pol-theta inhibitors that exploit new vulnerabilities put in place by emerging PARPi resistance mechanisms Citation Format: Christopher Lord. Mechanisms of sensitivity and resistance to HRD targeting agents in breast cancer – PARPi and beyond [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED12-2.
Abstract GS1-06: Evaluation of the Breast Cancer Index in premenopausal women with early-stage HR+ breast cancer in the SOFT trial
Authors: Ruth O’Regan, Yi Zhang, Gini F. Fleming, Prudence Francis, Roswitha Kammler, Giuseppe Viale, István Láng, Meritxell Bellet Ezquerra, Hervé R. Bonnefoi, Sherene Loi, Marco Colleoni, Catherine A. Schnabel, Kai Treuner, Meredith Regan
Journal: Cancer Research (2023)

Abstract Background: The landmark Suppression of Ovarian Function Trial (SOFT) in premenopausal breast cancer patients revealed that the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy with either tamoxifen (T+OFS) or exemestane (E+OFS) reduces the risk of recurrence compared with adjuvant tamoxifen alone. The benefit from the addition of OFS was most clinically meaningful for patients at higher clinico-pathologic risk of recurrence. There are no biomarkers to aid decision-making about intensification of endocrine therapy with OFS and its resultant toxicities. The Breast Cancer Index (BCI) is a gene expression–based signature that stratifies patients based on the risk of overall (0-10 years) and late (post-5 years) distant recurrence (DR) and predicts the likelihood of benefit from extended endocrine therapy in early stage HR+ breast cancer. The purpose of this study is to assess BCI’s prognostic and predictive ability in premenopausal women randomly assigned to 5-years treatment with E+OFS or T+OFS vs T alone in the SOFT trial. Methods: All available FFPE tumor samples from the SOFT trial (n=1718 of 3047) were included in the study. BCI testing was performed blinded to clinical characteristics, treatment and outcome. Median follow-up was 13 years. Primary endpoint was breast cancer-free interval (BCFI). Secondary endpoints were distant recurrence-free interval (DRFI) and disease-free survival (DFS). Kaplan-Meier analysis and Cox proportional hazards regression models, stratified by prior chemotherapy and lymph node status, were used to evaluate the predictive performance of BCI (H/I) status (High vs Low), and secondarily H/I as a continuous score. Hypothesis testing for interaction was performed by stratified log-rank tests. Results: Tumor samples from 1687 (98%) patients (30.4% &amp;lt; 40 years, 64.1% T1, 50.1% G2, 65.8% N0, 85.5%% HER2-, 53.3% received prior chemotherapy) were successful in BCI testing and included in the final analysis. Patient characteristics in the translational cohort are representative of the parent SOFT trial. 42.4% of patients’ tumors had H/I-High status. Prognostic and predictive analyses are ongoing and will be presented at the meeting. Citation Format: Ruth O’Regan, Yi Zhang, Gini F. Fleming, Prudence Francis, Roswitha Kammler, Giuseppe Viale, István Láng, Meritxell Bellet Ezquerra, Hervé R. Bonnefoi, Sherene Loi, Marco Colleoni, Catherine A. Schnabel, Kai Treuner, Meredith Regan. Evaluation of the Breast Cancer Index in premenopausal women with early-stage HR+ breast cancer in the SOFT trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-06.
Abstract ED8-2: The role of advanced radiation technology in reducing toxicity
Authors: Melissa Mitchell
Journal: Cancer Research (2023)

Abstract Over the past decade, breast cancer radiotherapy has increasingly focused on techniques to improve treatment precision and limit toxicity. Surface guided radiotherapy and respiratory gating has allowed for improved cardiac sparing and the elimination of permanent skin tattoos in women receiving breast radiation, while rapid developments in the technological delivery of radiation via both volumetric arc therapy and proton beam radiation have shown promise in further improving target coverage and normal tissue sparing for breast cancer patients. Cutting edge innovations, including MR-guided radiotherapy and FLASH technology are now being explored as means to further improve treatment precision and decrease toxicity. The purpose of this talk is to highlight and discuss these advances in radiotherapy, review the existing evidence to support their use in the treatment of breast cancer, and detail specific patient populations that are most likely to benefit. Discussion will also focus on ongoing and future research aimed at improving our understanding and utilization of these novel advances in care. Citation Format: Melissa Mitchell. The role of advanced radiation technology in reducing toxicity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED8-2.
Abstract ED5-1: Early palliative care
Authors: Tara Kaufmann
Journal: Cancer Research (2023)

Abstract This education session will review early palliative care in oncology and applications in patients with metastatic breast cancer. This presentation provides an overview of the field of research in early palliative care for patients with advanced solid tumors and discusses considerations specific to breast cancer. The speaker will present current challenges that we face in integrating palliative care into our practice and future areas for clinical innovation and research in palliative care. The speaker will present practical tips for how breast oncologists can deliver early palliative care to patients. The speaker will present guiding principles on when to consider referral to interdisciplinary, specialty palliative care. Citation Format: Tara Kaufmann. Early palliative care [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED5-1.
Abstract F1-1: Tumor stroma in DCIS progression
Authors: Robert West
Journal: Cancer Research (2023)

Abstract The interaction between cancer cells and the surrounding stroma plays a significant role in tumor growth and progression. The rapidly growing field of study involving the tumor microenvironment is discovering stromal-specific genes and cells that participate in this process. In invasive breast cancer, transcriptional analysis of stroma derived samples has identified stromal gene expression features that are correlated with clinical outcome with features characteristic of angiogenesis, hypoxia, and inflammation. The role of the microenvironment in DCIS is less well studied and has significant variation across and within DCIS. The basement membrane and myoepithelial cell layers provide a barrier for the interaction between neoplastic cells and the tumor microenvironment. DCIS tumor cells may be variably exposed to the immune environment. An immune infiltration is common in some DCIS, including high grade DCIS with necrosis. How this influences the transition from DCIS to IBC is complex. Citation Format: Robert West. Tumor stroma in DCIS progression [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr F1-1.